PB2427: THE RISK FACTORS ON THE SEVERITY OF SARS-COV2 OMICRON VARIANT INFECTION IN PATIENTS WITH HEMATOLOGIC MALIGNANCIES AFTER ALLOGENEIC HEMATOPOIEITC STEM CELL TRANSPLANTATION
Authors: Zhihui LI, Qinlong Zheng, Lei Wang, Xianxuan Wang, Xiaopei Wen, Caiyan Zhang, Jingjing Wang, Teng Xu, 彤 吴
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: In December 2022, a SARS-CoV2 omicron variant pandemic occurred in China. Patients with hematologic malignancies after allo-HSCT are at high risk of morbidity and mortality from SARS-CoV2 due to disease itself and therapy-related immunodeficiency. Aims: To investigate the risk factors on the severity of omicron infection in allo-HSCT setting. Methods: Sixty-three patients with hematologic malignancies after allo-HSCT who diagnosed as a symptomatic SARS-CoV2 omicron infection in our hospital were included. The median age was 22 (1- 64) years old, and male to female was 1:1.1. Underlying diseases were AML (54.0%), ALL (42.9%) and NHL(3.1%). Transplant types were haploidentical (81.0%), matched related (15.9%) and unrelated (3.1%). Omicron infection was confirmed by nucleic acid amplification testing. The severity of illness categories was defined as mild, moderate, severe and critical based on NIH COVID-19 Treatment Guidelines. Before transplant, more than 900 germline predisposition gene variants associated with hematologic and immunologic diseases were screened by NGS and analyzed according to American College of Medical Genetics and Genomics guidelines. Class I genetic variants were defined as pathogenic and class II genetic variants were defined as likely pathogenic. Results: The median time from allo-HSCT to omicron infection was 8.5 (0.3-208.2) months, and 16 (25.4%) patients developed omicron infection within 100 days after transplant. The severity of omicron infection was mild (54.0%), moderate (31.7%), severe (9.5%), and critical (4.8%). Clinical features included abnormal chest imaging (46.0%), hypoxia (14.3%), and mechanical ventilation in intensive care unit (4.8%). The median time of viral nucleic acid turn to negative was 12 (3-46) days. By Feb. 25, 2023, with the median follow-up 70 (14-89) days, 3 patients died. No reactivation of omicron was observed in the patients with mild illness, but 33% of omicron reactivation was noted in the patients with more severe pattern. The risk factors of severe omicron infection were older age (P<. 0001), chronic GVHD (P=0.0195), concomitant bacterial infection (P<. 0001), low lymphocyte count (P=. 026), low C4/CD8 ratio (P=. 0091), low CD4 cell count (P=0.0057), low B cell count (P=. 0154). high CD3 ratio (P=. 0062), high CRP (P<. 0001), high serum ferritin (P=. 0023), and high D-dimer (P<. 0001). The median number of class I inborn errors of immunity related gene variants was 1 (0-5), and the median number of class II inborn errors of immunity related gene variants was 7 (2-13). Among class I inborn errors of immunity related gene variants, MPEG1 and TNFAIP3 were recurrent for more than 5 times. Among class II inborn errors of immunity related gene variants, BRCA2, FANCA, ATM, FANCI, CFTR and MEFV were the most common ones. The most common gene variants related to autoimmune diseases were MEFV, TNFAIP3, IL36RN and IFIH1. The gene variants related to autoimmune disease in more severe illness (moderate, severe and critical) were significantly higher than that in mild disease (55.33% vs.15.79%, p=0.0086). Conclusion: Our study has shown that omicron infection in allo-HSCT setting has resulted in more pneumonia and more reactivation in advanced infection pattern (moderate, severe, and critical). The risk factors of the severity of omicron infection include not only some clinical features (age, chronic GVHD, immunodeficiency, and inflammatory reaction) but also inborn errors of immunity related gene variants. Keywords: Allogeneic hematopoietic stem cell transplant, Risk factor, COVID-19, Hematological malignancy